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P2Y12 Inhibition Suppresses Proinflammatory Platelet-Monocyte Interactions.
Rolling, Christina C; Sowa, Marcin A; Wang, Tricia T; Cornwell, MacIntosh; Myndzar, Khrystyna; Schwartz, Tamar; El Bannoudi, Hanane; Buyon, Jill; Barrett, Tessa J; Berger, Jeffrey S.
  • Rolling CC; Department of Medicine, New York University Grossman School of Medicine, New York, New York, United States.
  • Sowa MA; Department of Oncology and Hematology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
  • Wang TT; Department of Medicine, New York University Grossman School of Medicine, New York, New York, United States.
  • Cornwell M; Department of Medicine, New York University Grossman School of Medicine, New York, New York, United States.
  • Myndzar K; Department of Medicine, New York University Grossman School of Medicine, New York, New York, United States.
  • Schwartz T; Department of Medicine, New York University Grossman School of Medicine, New York, New York, United States.
  • El Bannoudi H; Department of Medicine, New York University Grossman School of Medicine, New York, New York, United States.
  • Buyon J; Department of Medicine, New York University Grossman School of Medicine, New York, New York, United States.
  • Barrett TJ; Department of Medicine, New York University Grossman School of Medicine, New York, New York, United States.
  • Berger JS; Department of Medicine, New York University Grossman School of Medicine, New York, New York, United States.
Thromb Haemost ; 123(2): 231-244, 2023 Feb.
Article in English | MEDLINE | ID: covidwho-2234961
ABSTRACT

BACKGROUND:

Monocyte-platelet aggregates (MPAs) represent the crossroads between thrombosis and inflammation, and targeting this axis may suppress thromboinflammation. While antiplatelet therapy (APT) reduces platelet-platelet aggregation and thrombosis, its effects on MPA and platelet effector properties on monocytes are uncertain.

OBJECTIVES:

To analyze the effect of platelets on monocyte activation and APT on MPA and platelet-induced monocyte activation.

METHODS:

Agonist-stimulated whole blood was incubated in the presence of P-selectin, PSGL1, PAR1, P2Y12, GP IIb/IIIa, and COX-1 inhibitors and assessed for platelet and monocyte activity via flow cytometry. RNA-Seq of monocytes incubated with platelets was used to identify platelet-induced monocyte transcripts and was validated by RT-qPCR in monocyte-PR co-incubation ± APT.

RESULTS:

Consistent with a proinflammatory platelet effector role, MPAs were increased in patients with COVID-19. RNA-Seq revealed a thromboinflammatory monocyte transcriptome upon incubation with platelets. Monocytes aggregated to platelets expressed higher CD40 and tissue factor than monocytes without platelets (p < 0.05 for each). Inhibition with P-selectin (85% reduction) and PSGL1 (87% reduction) led to a robust decrease in MPA. P2Y12 and PAR1 inhibition lowered MPA formation (30 and 21% reduction, p < 0.05, respectively) and decreased monocyte CD40 and TF expression, while GP IIb/IIIa and COX1 inhibition had no effect. Pretreatment of platelets with P2Y12 inhibitors reduced the expression of platelet-mediated monocyte transcription of proinflammatory SOCS3 and OSM.

CONCLUSIONS:

Platelets skew monocytes toward a proinflammatory phenotype. Among traditional APTs, P2Y12 inhibition attenuates platelet-induced monocyte activation.
Subject(s)

Full text: Available Collection: International databases Database: MEDLINE Main subject: Thrombosis / COVID-19 Type of study: Prognostic study Limits: Humans Language: English Journal: Thromb Haemost Year: 2023 Document Type: Article Affiliation country: S-0042-1758655

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Thrombosis / COVID-19 Type of study: Prognostic study Limits: Humans Language: English Journal: Thromb Haemost Year: 2023 Document Type: Article Affiliation country: S-0042-1758655